Method for treating a patient having precancerous lesion with 4-phenylphthalazine derivatives

Abstract

Derivatives of 4-phenylphthalazine are useful for the treatment of patients having precancerous lesions. These compounds are also useful to inhibit the growth of neoplastic cells.

We claim:  
     
       1. A method of treating a patient in need of treatment having precancerous lesions sensitive to a compound of formula I, comprising administering to the patient a pharmacologically effective amount of a compound of formula I:                    
       wherein X stands for NH or O;  
       R 1  is selected from an alkyl group having 1 to 5 carbon atoms, an alkoxy group having 1 to 5 carbon atoms, a halogen atom, an alkoxycarbonyl group having 2 to 6 total carbon atoms, a carboxyl group, a cyano group, an alkylcarbonyl group having 2 to 4 total carbon atoms, a hydroxyl group and a trifluoromethyl group;  
       R 2  and R 3 , which may be identical or different (may also be the same as or different from R 1 ), each is selected from an alkyl group having 1 to 5 carbon atoms, an alkoxy group having 1 to 5 carbon atoms, a halogen atom, an alkoxycarbonyl group having 2 to 6 total carbon atoms, a carboxyl group, an alkylcarbony group having 2 to 4 total carbon atoms, a hydroxyl group and a trifluoromethyl group; and  
       each of l, m and n is an integer of zero to 3 (provided that l=1 to 3 and m=n=zero when X is O, and the case where l=m=n=zero is excluded when X is NH), each plural number of R 1 , R 2  and R 3  being identical or different when the integers l, m and n are two or more.  
     
     
       2. The method of claim  1 , wherein X is NH. 
     
     
       3. The method of claim  2 , wherein l=1 to 3 and m=n=zero. 
     
     
       4. The method of claim  3 , wherein R 1  is selected from an alkyl group, an alkoxy group, a halogen atom and a trifluoromethyl group. 
     
     
       5. The method of claim  3 , wherein R 1  is selected from an alkoxy group and a halogen atom. 
     
     
       6. The method of claim  5 , wherein R 1  is a halogen. 
     
     
       7. The method of claim  6 , wherein said compound is 1-(3-chloroanilino)-4-phenylpthalazine. 
     
     
       8. The method of claim  2 , wherein l=1 to 2, m=1 to 2 and n=zero. 
     
     
       9. The method of claim  2 , wherein l=1 to 2, m=zero and n=1 to 2. 
     
     
       10. The method of claim  2 , wherein 1=m=zero and n=1 . 
     
     
       11. The method of claim  1 , wherein X is O. 
     
     
       12. The method of claim  11 , wherein l=1 to 3 and m=n=zero. 
     
     
       13. The method of claim  12 , wherein l=1 to 2. 
     
     
       14. The method of claim  1 , wherein R 1  and R 2  are independently selected from an alkyl group, an alkoxy group, a trifluoromethyl group and a halogen atom. 
     
     
       15. The method of claim  14 , wherein R 3  is an alkyl group. 
     
     
       16. The method of claim  15 , wherein R 1  is selected from an alkoxy group and a halogen atom. 
     
     
       17. The method of claim  16 , wherein R 1  is a halogen atom. 
     
     
       18. The method of claim  17 , wherein m=n=zero and l=1 to 3. 
     
     
       19. The method of claim  18 , wherein X is NH. 
     
     
       20. A method for inhibiting the growth of neoplastic cells sensitive to compound of formula I, comprising exposing said cells to an effective amount of a compound of formula:                    
       wherein X stands for NH or O;  
       R 1  is selected from an-alkyl group having 1 to 5 carbon atoms, an alkoxy group having 1 to 5 carbon atoms, a halogen atom, an alkoxycarbonyl group having 2 to 6 total carbon atoms, a carboxyl group, a cyano group, an alkylcarbonyl group having 2 to 4 total carbon atoms, a hydroxyl group and a trifluoromethyl group;  
       R 2  and R 3 , which may be identical or different (may also be the same as or different from R 1 ), each is selected from an alkyl group having 1 to 5 carbon atoms, an alkoxy group having 1 to 5 carbon atoms, a halogen atom, an alkoxycarbonyl group having 2 to 6 total carbon atoms, a carboxyl group, an alkylcarbony group having 2 to 4 total carbon atoms, a hydroxyl group and a trifluoromethyl group; and  
       each of l, m and n is an integer of zero to 3 (provided that l=1 to 3 and m=n=zero when X is O, and the case where l=m=n=zero is excluded when X is NH), each plural number of R 1 , R 2  and R 3  being identical or different when the integers l, m and n are two or more.  
     
     
       21. The method of claim  20 , wherein l=1 to 2, m=n=zero and X=NH. 
     
     
       22. The method of claim  21 , wherein R 1  is selected from an alkyl group, an alkoxy group, a halogen atom or a trifluoromethyl group. 
     
     
       23. The method of claim  22 , wherein R 1  is selected from an alkoxygroup and a halogen atom.